The overall goals of the Mayo Clinic Urology O'Brien Research Center are to develop new diagnostic strategies in order to accurately phenotype patients and thus apply improved individualized management strategies. We will pursue these goals via 4 interlinked multidisciplinary projects. Important and timely aims of the Mayo Clinic O'Brien Urology Research Center include: 1) Develop and validate a comprehensive low-dose stone-characterization exam using clinical dual-energy CT techniques in order to predict stone fragility, and to develop new CT methods capable of detecting the earliest possible precursor lesions. 2) Determine factors that produce NL precursor lesions including Randall's plaques and tubular plugs. 3) Define specific factors that increase the risk of kidney stones and their recurrence, and develop clinical prediction tools to help clinicians identify high-risk patients. 4) Define environmental and genetic factors that influence oxalate transport and crystallization in a novel high throughput Drosophila model. This proposal is highly responsive to the O'Brien Urology Research Center RFA bringing together truly multidisciplinary group of experienced clinicians and basic scientists to conduct translational research. Each project is multidisciplinary, and clinical, translational and basic research is each well represented. Further, all projects have clear clinical relevance and will impact our understanding of nephrolithiasis and our ability to care for patients. The Mayo Clinic has a unique collection of resources such as the Rochester Epidemiology Project; funded laboratories with expertise in genetics, proteomics and transport physiology; large patient volumes; and the CT Imaging Innovation Center which can be applied to this common yet understudied disorder. Through this O'Brien Center, existing clinical and basic science expertise in urology, nephrology, radiology, epidemiology, genetics and physiology will work in synergy to foster rapid progress.